Turnover and Recycling of the Peptidoglycan-Wall Teichoic Acid Complex in Gram-Positive Bacteria

• Applicants: Professor Dr. Christoph Mayer; Professor Dr. Alexander Titz
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms ; Biological and Biomimetic Chemistry
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 556461691

The cell wall of Gram-positive bacteria consists of two polymers, the peptidoglycan (PGN) and the covalently attached wall teichoic acids (WTAs). Together they form an extensive network, the PGN-WTA complex, that covers the cell membrane and protects the bacterial cell against environmental insults and osmotic lysis. During bacterial growth the PGN-WTA complex is steadily degraded in a process referred to as cell wall turnover, and the released cell wall fragments are eventually reutilized (i.e., recycled). The turnover and recycling metabolic pathways of the PGN-WTA complex in Gram-positive bacteria have so far been insufficiently understood due to the lack of suitable substrates for the identification and characterization of the key enzymes within these pathways. We will overcome this obstacle by the synthesis of readily detectable substrates that will allow to shed light on these processes in the Gram-positive model bacterium Bacillus subtilis. This will enable us to characterize and mechanistically assess unique glycosidases that have been identified in our groups recently. Moreover, we aim to identify and characterize novel enzymes that degrade the PGN-WTA complex. Particularly, teichoic acid degrading enzymes, so called teichoicases, are mostly unknown and the fate of the released teichoic acid fragments remains enigmatic. A better understanding of this process has far broader implications than simply expanding our knowledge of bacterial physiology. It is fundamental to understand how bacteria achieve a steady renewal of their cell wall, while preserving cell shape and integrity. It also allows gaining better insights into bacterial differentiation processes, such as the transition from growth to starvation/stationary phase and biofilm formation. Since cell wall autolysis plays a crucial role in the bactericidal action of antibiotics, our research will help deepen our understanding of antibiotic susceptibility and resistance. Further, it has implications for the optimization of biotechnological processes, since the cell wall recycling metabolism impacts autolysis, biomass synthesis rates and thus product yields.

• DFG Programme: Research Grants